Abstract

The process of B cell spreading and the formation of signalling BCR microclusters are critical to the effective activation of B cells. These processes are dependent on the actin cytoskeleton; however the molecular pathways leading to reorganization of the actin cytoskeleton upon B cell encounter with membrane-bound antigen are poorly understood. Recent work has highlighted a potential role for the novel ion channel protein Transient receptor potential cation channel, subfamily M, member 7 (TRPM7) in actomyosin reorganization. Intriguingly, this protein also contains a kinase domain, and thus, TRPM7 may play an important role in receptor-mediated signal transduction by phosphorylating downstream effector molecules. Interestingly, studies in B cells have implicated TRPM7 kinase in the regulation of phospholipase C (PLC), a key BCR signalling molecule and critical regulator of B cell spreading and the formation of BCR microclusters. Here, we show that TRPM7 plays a critical role in the early events of B cell activation through both its ion channel and kinase functions. B cells deficient in TRPM7 or expressing a point mutation which abolishes phosphotransferase activity show increased antigen accumulation and prolonged BCR signalling. Our data suggests this is likely due to altered actomyosin organization and defective antigen internalization.